Amount, rate of secretion and composition of saliva are modified by both sympathetic and parasympathetic receptor systems. The key neurotransmitters involved include norepinephrine, acetylcholine, substance P and VIP. Stimulation of specific cell membrane receptors by the neurotransmitters transmits signals through intracellular messengers (cations, nucleotides, phospholipid derivatives) to structures and enzymes within the cell. Ascorbate which is present in salivary glands in high concentrations is closely associated with the metabolism of these neurotransmitters and the signal transduction pathways, lending support to the hypothesis that ascorbate deficiency may impair receptor responsiveness and signal transductive events. The proposed study, using the guinea pig, an animal dependent solely on dietary sources for ascorbate, will examine effects of prolonged marginal vitamin C deficiency on submandibular gland muscarinic-cholinergic receptor density as assessed by [3H] - QNB binding, intracellular Ca2+ levels and inositol trisphosphate accumulation, and how these correlate with stimulated salivary flow rate and protein composition. Age- and sex- matched guinea pigs, pair-fed adequate vitamin C diet of the same physical consistency as the deficient diet, will serve as controls. The health relatedness of this project is underscored by the observation that virtually all the factors, including aging, drug ingestion, ionizing radiation, stress, smoking, autoimmune diseases, various pathological states, and other seemingly unrelated conditions often implicated in the causation of xerostomia all increase tissue requirement for ascorbate. Depending on race and income level, no less than 23-42% of the free-living elderly in the U.S. are ascorbic acid deficient. This study will therefore provide valuable clues for prevention and better management of dry mouth which exerts profound negative effects on a patient's quality of life, affecting dietary habits, speech, taste acuity, oral health, tolerance to dental prostheses, and psychological well-being (80).